The goal of this continuation Gastroenterology Research Training Program proposal is to prepare M.D., Ph.D., or M.D./Ph.D. postdoctoral fellows for careers as independent investigators in academic Gastroenterology. A diverse, experienced faculty will provide the opportunity to learn contemporary methods of cellular and molecular biology or clinical research by mentorship in one of five broad areas: A) Injury, Fibrosis Signaling & Gene Regulation; B) Cancer Biology & Genetics; C) Immunology and Virology; D) Molecular Basis of Metabolism, Development & Stem cells; or E) Patient-oriented Clinical Investigation in Hepatobililary and Gastrointestinal Diseases. The training will provide a solid foundation for future success in investigative Gastroenterology. To do so, expert faculty have been recruited from the Divisions of Gastroenterology, Liver Diseases, Nephrology, Hematology/Oncology, Infectious Diseases, Clinical Immunology and Endocrinology, and from two other Departments and six Research Institutes and Centers. Trainees will enter the program from one of four sources: 1) Following completion of least 18 months of clinical Gastroenterology fellowship at the Mount Sinai School of Medicine; 2) Following completion of a clinical Gastroenterology fellowship plus a year of clinical Hepatology at the Mount Sinai School of Medicine; 3) After the awarding of a Ph.D. degree in life sciences, or 4) Following completion of a Medicine Residency for exceptional candidates. Trainee candidates will devote a minimum of two years to training in either laboratory- or patient-based research. Each year this grant will continue support 3 trainees at the PGY 4 - PGY 6 level. The strong productivity and academic career choices of the grant's trainees to date reinforce the success of this 10 yr-old program. At least 90% of trainees' time will be devoted to working in the laboratory or clinical setting on an individualized research project under the guidance of faculty mentor(s). In addition, all trainees participate in weekly laboratory or clinical group meetings, attend relevant divisional, departmental and institutional research-oriented conferences, and enroll in specifically designed coursework in laboratory or clinical investigative methods. This integrated proposal emphasizing translational research will train future academic leaders in investigative gastroenterology. Such training will be essential to enable advances in the care of tens of million Americans affected by gastrointestinal and hepatobiliary diseases, including new approaches to the clinical management of affected patients through rigorous training. PUBLIC HEALTH RELEVANCE: The enlarging burden of gastrointestinal and liver diseases requires accomplished scientists who can make fundamental discoveries of pathogenesis and translate them into new treatments. This integrated proposal emphasizing translational research will train future academic leaders in investigative gastroenterology who can enable advances in the care of tens of million Americans affected by gastrointestinal and hepatobiliary diseases, including new approaches to the clinical management of affected patients through rigorous training.